Objective: Varenicline was approved by the FDA in 2006. In 2009, based largely on case reports, the FDA issued a warning of possible adverse neuropsychiatric effects including depression and suicidal thoughts and behavior for varenicline and bupropion. Prospective trials of varenicline have not reported increased incidence of psychiatric adverse events other than sleep disturbance, but smokers with major mental illness have been excluded from large prospective trials of varenicline to date. We sought to evaluate the effect of a standard open-label 12-week varenicline trial on prospectively assessed safety and smoking outcomes in adults with stable, treated schizophrenia spectrum disorder and nicotine dependence. Methods: One-hundred twelve stable outpatients who smoked 10 or more cigarettes/day participated in a 12-week open-label smoking cessation trial of varenicline and weekly group cognitive behavioral therapy. Participants took varenicline for 4 weeks before attempting cessation. Trained raters collected safety and smoking outcome data weekly. Results: Participants demonstrated improved psychotic symptoms, depressive symptoms, and nicotine withdrawal symptoms from baseline to week 12 or early termination. At the end of 12 weeks open-label treatment, the 14- and 28-day continuous abstinence rates were 47.3% and 34%, respectively. Expired carbon monoxide declined significantly during treatment in those who did not achieve abstinence. Conclusions: This prospective study suggests that varenicline may be well tolerated and effective for smoking cessation in combination with group cognitive behavioral therapy in stable outpatients with schizophrenia, a group with high rates of smoking and smoking-attributable morbidity and mortality. This clinical trial is registered at www.clinicaltrials.gov as trial #NCT00621777.
Bibliographical noteFunding Information:
Drs. Pachas, Nino-Gomez, Lando, Mueser, Pratt, and Hoepp-ner and Ms. Carlini have no financial relationships with commercial interests. Dr. Evins has received research grant support from Pfizer, Janssen, GlaxoSmithKline, EnVivo Pharmaceuticals, and Bowman Family Foundation and honoraria from Reed Medical Education and has advisory/consultant relationships with Euthymics, Pfizer, and Boehringer Ingelheim. Dr. Rigotti has received research grant support from Pfizer and Nabi Biopharmaceuticals and honoraria from UpToDate and is an unpaid consultant for Pfizer and Free and Clear. Dr. Goff has served as a consultant or advisor to Merck, Bristol-Myers Squibb, Wyeth, Organon, Xytis, XenoPort, Proteus, Vanda, AstraZeneca, Forest Labs, Pfizer, Indevus Pharmaceuticals, Lundbeck, Ortho-McNeil-Janssen, Schering-Plough, Eli Lilly, Takeda, Biovail, Solvay, Hoffmann-La Roche, Cypress, Dainippon Sumitomo Pharma, Abbott Laboratories, Genentech, and Endo Pharmaceuticals. He served on a data safety monitoring board for Otsuka and Wyeth. He has received research grant funding from Pfizer, Novartis, Janssen, and GlaxoSmithKline. Dr. Achtyes has received research support from AssureRx Health, Eli Lilly, Novartis, and Ortho-McNeil-Janssen. Dr. Cather has received compensation as a consultant for United BioSource Corporation and as a speaker for the MGH Academy.
This study was supported by NIDA R01 DA021245, Smoking Cessation and Relapse Prevention in Patients with Schizophrenia (Evins) and NIDA K24 DA030443 (Evins). Study medication was provided by Pfizer, Inc. This research was presented in part at the 2009 Annual meeting of the Society for Research on Nicotine and Tobacco, Dublin, Ireland.
- adverse events
- open label
- smoking cessation